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For the first time ever, a desi scientist creates a virtual liver | India News

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At its core, drug research is about two things: the processes that cause disease and how they can be altered. The answer lies in a maze of biological responses, chemical reactions, and adventitious hazards. It’s as difficult as it sounds: it takes about 50,000 visits for a drug to hit the market. But what if the long trial and error didn’t need any real human or animal?
For the first time, an Indian researcher has created a “virtual liver” that does just that.
“In basic terms, you need to find out what behavior of an organ you are interested in being able to predict,” explained Kalyanasundaram Subramanian, who developed the model together with his team. Then, it is necessary to map the biochemical pathways linked to that behavior. “If you can do that, you represent those paths in mathematical equations.” Basically, a replica of complex biological systems is translated into mathematical models.
Until now, digital hearts and virtual kidneys have been working, but this is the first time that a liver has been successfully modeled. The principle, the article says, is that if the normal state of a liver can be modeled in this way, any alteration of that state can be considered a pathological state. After that, one can find out, for example, how an organ behaves when someone is fasting, sleeping or infected; the possibilities are endless. But the most important thing, perhaps, is understanding how you might react to a drug.
“The chances that a drug molecule will eventually reach patients are so low that only one in 12 drug molecules that are tested in humans in clinical trials does so successfully on the market,” the article published in the ‘Journal of the Indian Institute of Science’ last month, it says. “Toxicity and lack of efficacy account for more than 60% of all drug failures.”
In his experiment, Subramanian looked at how a disease – type 2 familial progressive intrahepatic cholestasis, a progressive liver disease that eventually leads to organ failure – can be represented in the virtual liver and how a targeted drug could “treat” it. In those affected by the disease, the movement of bile salts is disrupted, leading to the accumulation of bile acid in the body. “Many children with this disease will die at a young age unless they can get a liver transplant,” the document said. The hypothesis, based on clinical studies, was that the introduction of a mechanism to reduce the reabsorption of bile salts in the intestine could solve this problem. When tested on “virtual patients”, by simulation, it worked.
Subramanian next looked at the effects of drug-induced liver injury. A big challenge in studying this has been the limitations posed by individual reactions: “A drug may appear safe when tested in healthy volunteers, but it can be problematic in sick individuals.” With the digital twin liver, it was possible to test the effects in large variations of “patients” without side effects.
“With this, research can be made safer and easier: by reducing the number of animals used in medical research, by selecting the right patient cohorts to conduct a trial, so that you only choose those who can benefit from the therapy, selecting the correct dosages in a trial so you can reduce side effects, ”Subramanian said. “It can bring therapies to the clinic faster by accelerating research using computer and technology-based methods, designing safer, more selective and better drugs through rational design driven by data and models.”
Could it also be used to better understand autoimmune disorders or cancer? “These diseases involve multiple organs, so a single twin organ would not work. You would need to create multiple organs and connect them to each other, ”Subramanian said. “But there are attempts, it’s a pretty hot field right now.”

Times of India

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